Comparison of in vitro and in vivo antimalarial activities of 9-phenanthrenecarbinols.

Analysis of the antimalarial activity of a selected series of 17 9-phenanthrenecarbinols against cultured strains of Plasmodium falciparum and against P. berghei in mice following oral administration indicated that the rankings of activities within the series were influenced by substituents on the 9-carbinol and the route of administration. Compounds with alkylamino-alkyl groups were ranked as most active by an in vitro screening system which assayed activity against chloroquine-sensitive and chloroquine-resistant strains of cultured P.

Plasmodium falciparum: mefloquine resistance produced in vitro.

Camp and Smith strains of the human malaria parasite Plasmodium falciparum became resistant to mefloquine after continuous cultivation in the presence of the drug. The 50% inhibitory dose (ID(50)) values for mefloquine, as assessed by [(3)H]hypoxanthine incorporation, were found to have increased 4-fold, from 3 mug/l to 12 mug/l. The ID(50) values obtained by morphological examination of the cultures increased 10-fold.

2-Acetylpyridine thiosemicarbazones. 9. Derivatives of 2-acetylpyridine 1-oxide as potential antimalarial agents.

In view of the antimalarial activity in mice of 2-acetylpyridine thiosemicarbazones, a series of analogous 1-oxides was prepared for evaluation. Their synthesis was achieved by the reaction of 2-acetylpyridine 1-oxide with methyl hydrazinecarbodithioate to give methyl 3-[1-(2-pyridinyl 1-oxide)ethylidene]hydrazinecarbodithioate (II). Reaction of the latter intermediate with secondary amines afforded the desired 2-acetylpyridine 1-oxide thiosemicarbazones (III).

In vitro assessment of 2-acetylpyridine thiosemicarbazones against chloroquine-resistant Plasmodium falciparum.

A series of 2-acylpyridine thiosemicarbazones was evaluated in vitro against a chloroquine-resistant Plasmodium falciparum strain. Antimalarial activity was assessed by the inhibition of uptake of [G-3H]hypoxanthine by the parasites. Among the mono- and disubstituted derivatives tested, 13 of 17 had 50% inhibitory doses of less than 10 ng/ml.